BONE MARROW & STEM CELL TRANSPLANT

BRAIN CANCER

BREAST CANCER

CAR T-CELL THERAPY

ENDOMETRIAL CANCER

GASTRIC CANCER

GENITOURINARY CANCERS

GENOMIC TESTING

GI CANCERS

GYNECOLOGIC CANCERS

HEAD & NECK CANCERS

HEMATOLOGY

IMMUNOTHERAPY

LEUKEMIAS

LUNG CANCER

LYMPHOMAS

MET-TARGETED THERAPY

NTRK GENE FUSIONS

SARCOMA

SKIN CANCERS

SMALL CELL LUNG CANCER

THYROID CANCERS

NEWS

All News

Special Reports

CONFERENCES

Conference Coverage

Conference Listing

MEDIA

All Videos

Case-Based Peer Perspectives

Expert Perspective Virtual Tumor Board

Interviews

Investigator Perspectives

Medical World News

Podcasts

Precision Medicine

PUBLICATIONS

All Publications

Evolving Paradigms

Roundtable Meetings Spotlight

Targeted Therapies in Oncology

CME/CE

RESOURCES

Case-Based Roundtable Series

Clinical Trials

Partners

Precision Medicine Perspectives

Press Releases

Treatment Resources

SUBSCRIBE

eNewsletter

Targeted Oncology provides news, videos, and reviews on the rapidly evolving world of targeted therapies and immunotherapy for oncologists treating patients in a community setting.

About Us

Advertise

Contact Us

CureToday.com

CancerNetwork.com

OncLive.com

OncNursingNews.com

Do Not Sell My Information

Privacy

Terms & Conditions

Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways

Facebook

Linkedin

Twitter

YouTube

Instagram

Featured Clinical Focus

BTK Inhibitors: In-Focus

Biomarker-Driven Lung Cancer

Bone Marrow & SCT

CAR T-Cell Therapy

Chronic Lymphocytic Leukemia

EGFR-Positive Lung Cancer

Endometrial Cancer

Follicular Lymphoma

Lung Cancer

MPNs

Mantle Cell Lymphoma

Multiple Myeloma

Renal Cell Carcinoma

Small Cell Lung Cancer

Thyroid Cancers

Clinical Focus

Brain Cancer

Breast Cancer

Gastrointestinal Cancer

Genitourinary Cancers

Gynecologic Cancers

Head & Neck Cancers

Hematology

Leukemias

Lymphomas

Melanoma

Sarcoma

Skin Cancers

Spotlight

Case Based Peer Perspectives

1rem

Clinical

Findings from the phase 2 Study CDRB436G2201 trial have led the FDA to approve dabrafenib combined with trametinib for pediatric patients with BRAF V600E-mutated low-grade glioma who require systemic therapy.

FDA Approves Dabrafenib Plus Trametinib for Pediatric BRAF V600E-Mutant Low-Grade Glioma

Vorasidenib may break a 20-year gap in treatment advances for IDH-mutant low-grade glioma, according to phase 3 findings from the INDIGO study.

Vorasidenib Delays Disease Progression or Death in IDH+ Low-Grade Glioma

The FDA has granted the cell therapy temferon an orphan drug designation to treat patients with brain cancer.

FDA Gives Orphan Drug Designation to Temferon for Glioblastoma Multiforme

Based on the FDA’s review of a new drug application, a phase 2 study will evaluate the safety and efficacy of azeliragon for patients with glioblastoma.

FDA Okays Phase 2 Study of Azeliragon for Patients With Glioblastoma

In an interview with Targeted Oncology, Patrick Wen, MD, discussed precision medicine for adult gliomas, including present and future treatment options.

Present and Future Precision Medications Signal Promise for Adults With Glioma

Rupesh R. Kotecha, MD, chief of Radiosurgery and director of Central Nervous System Metastasis at Baptist Health Miami Cancer Institute, discusses a newer radiation modality known as pulse reduced dose rate radiation therapy.

Kotecha co-authored a study that used pulse reduced dose rate radiation therapy and presented the research at the American Society for Radiation Oncology (ASTRO) Annual Meeting.

 Pulse reduced dose rate radiation therapy is a very specific reirradiation approach, which has been used primarily in the central nervous system space for recurrent primary brain tumors. But it's also been explored in a couple of circumstances outside of the brain itself. Now, this research was previously limited to very few institutions who had experience with using this technique, and also who see this patient volume. Typically, patients with recurrent primary brain tumors traveled to specific centers of excellence or those who have clinical trials. And then sometimes those centers may not have clinical trials that the patient will be eligible for. But then we have a larger experience or volume of patients with that particular need.

 So, this was developed at a number of institutions, as one of those re-irradiation approaches to try and control the disease after somebody has progressed on multiple lines of systemic therapy. We had previously known at least in the limited series that had been done, that there was some aspect of disease control that looked very favorable, and the order of maybe six months or so longer in some series, shorter and other series.

 The purpose of our study was to do two things. Number one is to actually incorporate the prior radiation therapy plans, and then add the new reirradiation plans together to come up with those constraints, safety threat thresholds that could be used in the future when patients are undergoing radiation. The second goal was to basically pull the analyses from these different institutions so that we would know what [the] composite outcomes are, not just what does institution A or B, or C actually present or publish. But what happens when you pull all the outcomes together statistically, to look at what those outcomes could be across all of the institutions

Videos

Rupesh R. Kotecha, MD, discusses a newer radiation modality known as pulse reduced dose rate radiation therapy.



Understanding Pulse Reduced Dose Rate Radiotherapy 

The final patient with glioblastoma multiforme (GBM) has been enrolled in the ongoing phase 2 clinical trial of VAL-083, which is evaluating the efficacy, safety, and pharmacokinetics of the agent in patients who have been pre-treated with temozolomide (Temodar) prior to disease recurrence, according to a press release from Kintara Therapeutics, Inc.

VAL-083 is a first-in-class small molecule bifunctional alkylating agent that has the ability to cross the blood-brain barrier. VAL-083 was previously granted Orphan Drug Designation for GBM by the FDA as well as a Fast Track designation for the treatment of patients with recurrent GBM.

The study, which is being conducted at the MD Anderson Cancer Center in Houston, Texas, enrolled 83 patients into the recurrent arm to determine whether the drug will improve overall GBM survival. Of the 83 patients, 35 patients will receive 40 mg/m2/day of VAL-083 and 48 patients will receive 30mg/m2/day. Efficacy is determined by overall survival (OS) as well as progression-free survival (PFS). 

The second arm of the 2-arm, open label, biomarker-driven study enrolled 36 newly diagnosed patients who have undergone surgery and chemoradiation with temozolomide, are receiving VAL-083 as opposed to the standard of care of temozolomide for adjuvant therapy.

In a follow-up presented in November 2020, the median OS for the 77 evaluable patients who completed at least 1 treatment cycle was 7.6 months. The second arm of the study had a median PFS of 10.0 months. In the 30 mg/m2/day, group, 3 patients experienced a serious adverse event related to the treatment.

"Given the urgent need for improved treatment options for this deadly disease, we are pleased to have reached the very important milestone of full enrollment in the recurrent arm of this Phase 2 clinical study," said Saiid Zarrabian, chief executive officer, Kintara Therapeutics, in a press release.

Kintara Therapeutics Enrolls Final Patient in Phase 2 Clinical Trial of VAL-083 for Recurrent GBM. February 17, 2021; San Diego, CA. Accessed February 18, 2021. https://bit.ly/3jXTxEs

The final patient with glioblastoma multiforme has been enrolled in the ongoing phase 2 clinical trial of VAL-083, which is evaluating the efficacy, safety, and pharmacokinetics of the agent in patients who have been pre-treated with temozolomide prior to disease recurrence.

News

Phase 2 Study of VAL-083 Trial Reaches Target Enrollment of Patients With Glioblastoma Multiforme

Joshua Palmer, MD, radiation oncologist, The James Cancer Hospital and Research Institute, Wexner Medical Center at The Ohio State University, discusses a pooled analysis of 2 randomized clinical trials that compared how clinical outcomes and quality of life were impacted with stereotactic radiosurgery versus whole-brain radiation therapy (WBRT) in patients with brain metastases.

Palmer presented the results from the pooled analysis in a presentation during the 2020Society for Neuro-Oncology (SNO) Virtual Conference on Brain Metastases, held on August 14, 2020.

Due to the aggressive of radiation treatments, radiation oncologists have not been able to improve survival in patients being treated for brain metastases. Instead, the clinical outcomes typically impacted by radiation is tumor control, cognition, and quality of life in patients. Since overall survival is improved upon with the use of systemic therapies, such as targeted therapies, in order for radiation to sustain its role in treatment, radiation oncologists must focus on how they impact patients’ quality of life, Palmer stated. This was the goal of the pooled analysis.

The results showed that in patients who received WBRT there was a 2-year trend toward increased cognitive decline in 5 out of 6 cognitive measures, whereas patients who underwent stereotactic radiosurgery only had a decline in 2 out of the 6 cognitive measures. Both arms demonstrated a decline in delayed recall and delayed recognition. On the other hand, processing speed, executive function, and word association improved in the stereotactic radiosurgery arm versus the WBRT arm.

Joshua Palmer, MD, discusses a pooled analysis of 2 randomized clinical trials that compared how clinical outcomes and quality of life were impacted with stereotactic radiosurgery versus whole-brain radiation therapy in patients with brain metastases.

Conference News

Radiosurgery Improves Clinical Outcomes in Brain Metastasis Treatment

David Roberge, MD, associate professor at the University of Montreal and head of the Department of Radiation Oncology at the Centre Hospitalier de l'Université de Montréal–Notre Dame, discusses the current role of radiosurgery in the brain metastasis treatment paradigm, a topic he reviewed during a presentation at the 2020 Society of Neuro-Oncology Conference on Brain Metastases.

Radiation is most commonly used as treatment of brain metastasis, said Roberge. A one-time radiosurgery procedure is more attractive to patients though, Roberge notes, because it offers the same treatment effect as radiotherapy alone but does not require repeat visits to the clinic. What radiation oncologists do not know about radiosurgery is how it impacts overall survival and quality of life in patients.

Recent studies have shown, however, that radiosurgery may positively impact cognitive outcomes in patients with multiple brain metastases considering that outcomes were better for patients who received radiosurgery compared with whole-brain radiation. Contrarily, Roberge hypothesizes that the more brain metastases that are treated with radiosurgery, the higher the risk in interfering with positive treatment outcomes.

David Roberge, MD, discusses the current role of radiosurgery in the brain metastasis treatment paradigm, a topic he reviewed during a presentation at the 2020 Society of Neuro-Oncology Conference on Brain Metastases.


Roberge Explains the Role of Radiotherapy in Treatment of Brain Metastasis

David Reardon, MD, clinical director for the Center for Neuro-Oncology and institute physician at the Dana-Farber Cancer Institute, and professor of medicine at Harvard Medical School, discusses the interim results and toxicity with INO-5401 and INO-9012 delivered intramuscularly with electroporation in combination with cemiplimab (Libtayo) in patients with newly diagnosed glioblastoma.

According to Reardon, these agents were well tolerated and there were no significant adverse effects (AEs) associated with the vaccine. Cemiplimab showed the usual spectrum of AEs that are usually associated with PD-1 inhibitor therapies and there were no unexpected or new toxicities in the context of treating patients with glioblastoma.

There were 52 patients treated on the trial; 32 in cohort A, which was the O6-methylguanine-DNA methyltransferase (MGMT) unmethylated group, and 20 in cohort B, which was MGMT methylated. All of these patients had a reassuring safety profile, Reardon says.

It is too early to assess the efficacy of the regimen in these patients, but initial results showed encouraging progression-free survival results at 6 months and overall survival at 12 months. They were both higher than what would be expected at the time of the interim analysis for patients with newly diagnosed disease, according to Reardon. It is still too early to draw conclusions with these data.

<< View more resources and information regarding brain cancer

David Reardon, MD, discusses the interim results and toxicity with INO-5401 and INO-9012 delivered intramuscularly with electroporation in combination with cemiplimab in patients with newly diagnosed glioblastoma.

Interim Analysis Demonstrates Reassuring Toxicity Profile for Glioblastoma

Mustafa Khasraw, MD, medical oncologist, neuro-oncologist, and deputy director of the Center for Cancer Immunotherapy at the Duke Cancer Institute, discusses a follow-up trial to the VERTU study (NCT02152982) for patient with methylated or unmethylated MGMT (O6-methylguanine-DNA methyltransferase) glioblastoma who responded well to temozolomide (Temodar) chemotherapy and radiation.

For the follow-up trial, after receiving temozolomide and radiation, patients were randomized to veliparib (ABT-888), a PARP (poly (ADP-ribose) polymerase) inhibitor, with temozolomide and radiation or placebo with temozolomide and radiation. This study has a larger number of patients than the VERTU trial and has been completed, according to Khasraw. He expects the results will come out sometime over the year of 2020. The patients included in this trial were those left out the original VERTU trial.

Khasraw says that moving forward, there needs to be biomarkers and subsets of patients identified for this setting; specifically, those who will benefit from a PARP inhibitor, if there is a benefit at all. He also suggests that other treatments be explored, such as combinations of immunotherapy for patients with glioblastomas.

<< View more information on the VERTU trial

Mustafa Khasraw, MD, discusses a follow-up trial to the VERTU study for patient with methylated or unmethylated MGMT glioblastoma who responded well to temozolomide chemotherapy and radiation.

Further Investigation of Veliparib Underway for Glioblastoma

Arati Desai, MD, co-director of the University of Pennsylvania Brain Tumor Cancer Program Center and assistant professor of Clinical Medicine, at the Perelman School of Medicine, University of Pennsylvania, explains how the results from the phase III STELLAR trial will enhance knowledge of anaplastic astrocytoma (AA).

When treatment advances are sought, the therapies that are needed are those that improve upon the standard of care. There are good agents available for the treatment of AA, but the drugs are older and, at times, cause intolerable toxicity and offer limited benefit.

Arati Desai, MD, explains how the results from the phase III STELLAR trial will enhance knowledge of anaplastic astrocytoma.

New Combination Builds Upon Existing Therapies for Anaplastic Astrocytoma

Mustafa Khasraw, MD, deputy directoy, medical oncologist and nuerologist, Duke Center for Cancer Immunotherapy, Duke Cancer Center, Duke Health, discusses the purpose of the phase II VERTU study and shares key takeaways from his presentation at the 2019 Society for NeuroOncology Annual Meeting

The study randomized patients to standard treatment (radiotherapy) plus temzolomide chemotherapy for glioblastoma or the combination of PARP inhibitor veliparib (ABT-888) with radiotherapy followed by temzolomide in combination with veliparib, which was the experimental arm of the trail. The study included patients with glioblastoma who have a poor prognosis due to an unmethylated enzyme called MGMT. The purpose of the experiment was to make DNA-repair inefficient so that cancer cells would be eliminated.

The experimental combination did not improve survival in patients with unmethylated MGMT glioblastoma despite previous signals of activity in animal subjects, which was the rationale for the VERTU study.

Mustafa Khasraw, MD, discusses the purpose II VERTU study and shares key takeaways from his presentation at the 2019 Society for NeuroOncology Annual Meeting.

Khasraw Discusses Veliparib Combination Used in Patients With Unmethylated MGMT Glioblastoma

An interim analysis of the phase II study of palbociclib (Ibrance) for the treatment of patients with brain metastases harboring CDK alterations (NCT02896335) was presented at the 2019 Society for NeuroOncology Annual Meeting by Priscilla K. Brastianos, MD, director of the central nervous system brain metastasis program, Massachusetts General Hospital.

The study had a Simon 2-stage design. Fifteen patients were enrolled in the first stage of the trial. If at least 2 patients showed an intracranial clinical benefit, investigators would then proceed with the second stage of the study. In stage 2, if 6 out of 30 participants had a clinical benefit intracranially, then the treatment would be worthy of further study.

Brastianos says the trial was a genomically-guided trial in which patients were targeted based on the alterations found in their brain metastasis. Patients whose brain metastasis tissue harbored alterations in the CD4 pathway were given, CDK inhibitor, palbociclib. The results of this analysis showed that 8 out of the first 14 evaluable patients had clinical benefit intracranially.

An interim analysis of the phase II study of palbociclib for the treatment of patients with brain metastases harboring CDK alterations was presented at the 2019 Society for NeuroOncology Annual Meeting by Priscilla K. Brastianos, MD, director of the central nervous system brain metastasis program, Massachusetts General Hospital.<br />
&nbsp;

Palbociclib Shows Promise for Treatment of Brain Metastases Harboring CDK Alterations

TRK as Ideal Candidate for Targeted Therapy

Scientific Rationale for Development of TRK Inhibitors

Early Development of TRK Inhibitor-Larotrectinib

Efficacy of TRKi-Larotrectinib Among Tumor Types

Safety and Efficacy Profile for TRKi-Larotrectinib

Patient Selection for TRKi-Larotrectinib

TRKi: High Response Rate in Patients With Primary CNS Disease

Entrectinib-A Multitargeted TKI

Entrectinib-Selective ROS Inhibition

Investigational Approaches for TRK-Fusion Cancers

NGS Testing to Detect TRK Fusions

Molecular Testing for RAI-Refractory Thyroid Cancer

Dirty Kinases in TRK-Fusion Malignancies

Prostate Cancer

Ovarian Cancer

Colorectal Cancer

Bladder Cancer

EGFR+ Lung Cancer

TRK Inhibitors: A Tumor Agnostic Approach to Treatment of Solid Tumors

Before the era of targeted therapy, before we had all these new drugs now, what was the standard of care after radioactive iodine? Was it docetaxel?

Actually, it wasn&rsquo;t docetaxel. Adriamycin was the only approved drug in 1974. Even though it was FDA approved, once we had CAT [computerized axial tomography] scans, it turned out they weren&rsquo;t responding. We had an FDA-approved drug that was not causing responses, so it was actually supportive care. This is really amazing. I mean, in our generation where there was nothing, and now all of a sudden, this is an agent.

When you look at lenvatinib compared with larotrectinibI mean adverse-effect-wise, profile-wise&mdash;how do you see that in comparison?

As you know, larotrectinib is very well tolerated, with dizziness being 1 of the primary issues. We do actually have patients who get myalgia, and it&rsquo;s not just if they don&rsquo;t take their drug on time. Unfortunately, it&rsquo;s sort of anticipatory, so we&rsquo;re going to have to work that out. I think that can be worked out by dosing, so we&rsquo;re going to probably learn how to adjust for that. In general, larotrectinib is very, very well tolerated. And even the dizziness in our patientseven though it didn&rsquo;t go away, some people say it gets better with longer treatment. In the patients for whom it didn&rsquo;t, 1 single-dose reduction and they still have a complete response. So it may not be that we need to have dizziness, and we can probably treat around that.

The other drugs can cause quite a bit of morbidity, like hand-foot skin reaction. With lenvatinib, there&rsquo;s a lot of hypertension. That&rsquo;s actually the No. 1 issue we have to manage. And that&rsquo;s not just grade 1; it&rsquo;s a significant proportion of grade 3. So hand-foot skin reaction with sorafenib and hypertension with lenvatinib, and then diarrhea in both casesthese impact people. Initially, we were thrilled, of course, to have drugs that are so effective. But I think toxicity profile does matter, especially because these patients live a long time now with their disease.

Marcia, you&rsquo;ve now treated probably many, many patients with

fusions in thyroid. When you look at the data sets and your own experience, what is the overall response in thyroid, in papillary thyroid, in some patients even anaplastic thyroid cancer?

There actually haven&rsquo;t been that many. There have been about 7 patients, and 1 of them was anaplastic. And they did very well compared with anaplastic. Their progression-free survival, I think, lasted on the drug about 6 months before they had some progression. Of course, that&rsquo;s a

wild-type patient who then got tested. That 6 months in anaplastic, for anybody who treats anaplastic thyroid cancer, it turns out to be a good number because these patients on the other kinase inhibitors will progress by their first assessment. So it&rsquo;s probably active in anaplastic. I definitely would be testing every patient who has anaplastic thyroid cancer without a

Interestingly, in the differentiated, there have been about 5 or 6, and their responses have been great. Just as you&rsquo;ve seen across the board, we&rsquo;re talking a very high rate60% to 70%&mdash;and we&rsquo;re talking deep responses. We&rsquo;re talking 80%. I think you point out it was ones on the phase I, a complete response. These are really amazing.

The 1 thing I actually would like to point out about thyroid cancer is that we have a new adolescent thyroid cancer program, and it turns out there are a growing numberwell, not a growing number, we&rsquo;re just more aware of them now&mdash;of adolescents who have RAI-refractory thyroid cancer. Almost all those patients have

. I think that we don&rsquo;t have a lot of experience with them. I have 3 or 4 patients in my clinic who don&rsquo;t need systemic therapy yet. But as soon as it starts to grow, this will be a great drug for them, because they&rsquo;ll be able to go to school and have a great quality of life. I might really go to larotrectinib before going to the other FDA-approved drugs, just because adverse-effect profiles in kids is really going to make a difference.